Blocking a killer hook

Smoking is linked to one in five US deaths a year. But legal and technological changes are in sight to dramatically reduce nicotine, the addictive property in tobacco products.

By Diedtra Henderson, Globe Staff | July 30, 2007

WASHINGTON -- Public health advocates are within striking distance of a goal that has eluded them for generations: widespread availability of cigarettes with nicotine levels that are too low to become addictive.

They are pinning their hopes on a bill sponsored by Senator Edward M. Kennedy, Democrat of Massachusetts, which would give the Food and Drug Administration sweeping regulatory authority over tobacco products.

That new power would include the ability to reduce cigarettes' harm, which many say eventually could lead to the market being flooded with cigarettes that contain less nicotine -- the chemical component that makes them addictive. While the FDA can regulate nicotine-replacement therapies now, it lacks regulatory oversight over cigarettes and smokeless tobacco, and it can't prevent tobacco sales to youths.

Already, near rolling hills where generations of North Carolina farmers have grown traditional tobacco plants, a small biotech firm has planted tobacco specially engineered to eliminate most nicotine. And tobacco research labs, like one at the University of California, are testing experimental cigarettes in hardcore smokers to see if gradually lowering nicotine helps them kick the habit.

The moves run counter to recent tobacco industry efforts that secretly boosted nicotine in cigarettes.

The Kennedy bill is one of many tobacco-related proposals being considered by the Senate, but it stands the best chance of passage. On Wednesday, the bill is expected to clear a final hurdle before heading to the full Senate.

According to the American Cancer Society, to bacco use causes nearly one in five deaths in the United States annually -- about 440,000 -- and smoking increases healthcare costs by $167 billion a year. While cigarette use has fallen to its lowest level since World War II, more than 20 percent of Americans still smoke.

In considering the role the FDA might play in reducing smoking, Gregory N. Connolly, a professor at the Harvard School of Public Health, points to industrial use of cocaine in the 1900s. Manufacturers liberally added the drug to products as diverse as Coca-Cola and cough medicine. But after the FDA set purity standards, then restricted sales, cocaine disappeared from consumer products.

With nicotine levels in tobacco, "we're looking at a similar analogy," Connolly said. He predicts FDA oversight could result in wide sales of nonaddictive cigarettes within 20 years.

Dr. Neal L. Benowitz, a researcher at the University of California-San Francisco, believes it is possible to create a less addictive cigarette without sacrificing taste. Because smokers would puff fewer of them, their health risks would be reduced.

"The main harm from nicotine is the addiction part. The main health concerns come from the other parts of the smoke -- not to say that nicotine is totally benign," Benowitz said.

Currently, smokers inhale about 1 to 2 milligrams of nicotine per cigarette. That's about one-tenth of the 10 to 15 milligrams of total nicotine in each cigarette.

Benowitz's aim is to reduce nicotine delivery to less than one-tenth of a milligram per cigarette, weaning smokers from the chemical responsible for their urge to light up.

A few years ago, Benowitz tested his theory in a pilot project involving 20 volunteer smokers who smoked at least 10 cigarettes per day and who had smoked at least a decade.

His lab is equipped with the kind of specialized ventilation used in bioterror research facilities to stop killer germs from escaping, to safely permit smoking indoors.

The cigarettes, manufactured by Philip Morris USA for research purposes, look like Marlboros and contain the same levels of tar.

The smokers were given five different experimental cigarettes that, over six weeks, exposed them to less and less nicotine.

"They didn't smoke more than they had before," Benowitz said. At the end of the study, one-quarter quit smoking.

A tobacco specialist at the Boston University School of Public Health who discussed the soon-to-be-published study with Benowitz over lunch points to a different statistic.

"Three-quarters went back to their regular cigarettes," said Dr. Michael Siegel. "It was an unacceptable cigarette. People were not willing to smoke it."

That's the market peril faced by such companies as 22nd Century Ltd., a New York biotech that tinkered with tobacco to create plants that reduce nicotine levels to almost zero without raising levels of other harmful chemicals.

Vector Tobacco licensed that technology to create cigarettes it began marketing in 2003 under the Quest brand. After discussing its phase II clinical trial results with the FDA, Vector announced it would scrap plans to seek FDA approval of Quest as a smoking-cessation tool.

The decision was based on "the projected significant additional time and expense involved in seeking such approval," the company said in a filing last November with the Securities and Exchange Commission.

22nd Century's president said the biotech hopes to pick up where Vector left off, completing late-stage trials in humans. It hopes that FDA regulation of tobacco products will spike demand among cigarette manufacturers for their tobacco.

Kennedy's bill has the backing of dozens of public health advocacy organizations who consider his legislation the best way to reduce nicotine levels in cigarettes, silence advertising aimed at children, and eliminate candy-flavored cigarettes that may attract children to smoking. The measure would add 2.5 cents to the price of a pack of cigarettes to fund additional FDA staffing to regulate tobacco.

"To reduce [nicotine] actually would be harmful," Siegel said. "That person is going to compensate by smoking more. The only benefit of reducing nicotine is to completely take it out."

And then there is a bill that will soon be introduced by Senator Richard Burr, Republican of North Carolina, a major tobacco-producing state. Burr says he wants to lower the level of chemicals in cigarettes that are directly linked to cancer, instead of regulating nicotine levels.

Advocates who champion nicotine reduction are "misguided in believing that nicotine is the key to reduced harm," Burr said. "Taking constituents out of the process of combustion -- benzene and other things -- are, in fact, the greatest benefit that we can make to health."

Harvard's Connolly, whose research shined the spotlight on the industry's deliberate efforts to increase nicotine in cigarettes, strongly disagrees.

"If we get into that trap, we'll be debating this issue for another 200 years," he said. "What the industry doesn't want us talking about is nicotine. That's where the profits are."